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Journal of Virology, November 2003, p. 11563-11577, Vol. 77, No. 21
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.21.11563-11577.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Multigene DNA Priming-Boosting Vaccines Protect Macaques from Acute CD4+-T-Cell Depletion after Simian-Human Immunodeficiency Virus SHIV89.6P Mucosal Challenge

N. A. Doria-Rose,1,2 C. Ohlen,3 P. Polacino,4 C. C. Pierce,1,{dagger} M. T. Hensel,1 L. Kuller,4 T. Mulvania,3 D. Anderson,4 P. D. Greenberg,3 S.-L. Hu,2,4,5 and N. L. Haigwood1,2,6*

Seattle Biomedical Research Institute,1 Department of Pathobiology,2 Department of Immunology,3 Washington National Primate Research Center,4 Department of Pharmaceutics,5 Department of Microbiology, University of Washington, Seattle, Washington6

Received 17 March 2003/ Accepted 16 July 2003

We evaluated four priming-boosting vaccine regimens for the highly pathogenic simian human immunodeficiency virus SHIV89.6P in Macaca nemestrina. Each regimen included gene gun delivery of a DNA vaccine expressing all SHIV89.6 genes plus Env gp160 of SHIV89.6P. Additional components were two recombinant vaccinia viruses, expressing SHIV89.6 Gag-Pol or Env gp160, and inactivated SHIV89.6 virus. We compared (i) DNA priming/DNA boosting, (ii) DNA priming/inactivated virus boosting, (iii) DNA priming/vaccinia virus boosting, and (iv) vaccinia virus priming/DNA boosting versus sham vaccines in groups of 6 macaques. Prechallenge antibody responses to Env and Gag were strongest in the groups that received vaccinia virus priming or boosting. Cellular immunity to SHIV89.6 peptides was measured by enzyme-linked immunospot assay; strong responses to Gag and Env were found in 9 of 12 vaccinia virus vaccinees and 1 of 6 DNA-primed/inactivated-virus-boosted animals. Vaccinated macaques were challenged intrarectally with 50 50% animal infectious doses of SHIV89.6P 3 weeks after the last immunization. All animals became infected. Five of six DNA-vaccinated and 5 of 6 DNA-primed/particle-boosted animals, as well as all 6 controls, experienced severe CD4+-T-cell loss in the first 3 weeks after infection. In contrast, DNA priming/vaccinia virus boosting and vaccinia virus priming/DNA boosting vaccines both protected animals from disease: 11 of 12 macaques had no loss of CD4+ T cells or moderate declines. Virus loads in plasma at the set point were significantly lower in vaccinia virus-primed/DNA-boosted animals versus controls (P = 0.03). We conclude that multigene vaccines delivered by a combination of vaccinia virus and gene gun-delivered DNA were effective against SHIV89.6P viral challenge in M. nemestrina.

* Corresponding author. Mailing address: Seattle Biomedical Research Institute, 4 Nickerson St., Seattle, WA 98109. Phone: (206) 284-8846, ext. 338. Fax: (206) 284-0313. E-mail: Nancy.Haigwood{at}sbri.org.

{dagger} Present address: Hollister-Stier Laboratories, LLC, Spokane, Wash.

Journal of Virology, November 2003, p. 11563-11577, Vol. 77, No. 21
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.21.11563-11577.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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